Alveolar epithelial cell injury and repair in fibrotic lung disease

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Prof Monica Spiteri (Lung Research, University Hospital of North Staffordshire)

Problem Description

Pulmonary fibrosis (PF) is a devastating illness involving exaggerated lung scarring; with no efficacious therapy to modify its natural progressive clinical course. An estimated two-thirds of patients die within 2 to 4 years of diagnosis. Donated healthy lung transplants are used to replace fibrosed lungs, but need for transplants far outweighs available supply. Stem cell research currently offers tremendous promise for effective treatment of PF. However, clinical efficacy of stem cell–based strategies could be hampered by extracellular fibrotic factors driving disease processes at the target site. We hypothesise that PF-related abundance of profibrogenic factors such as Connective Tissue Growth Factor (CTGF) and Transforming Growth Factor (TGF-β1) drives progenitor alveolar epithelial cells (AEC) away from terminal differentiation conducive to local alveolar tissue regeneration; towards effector fibroblast/myofibroblast development.

This fundamental question needs addressing; it has implications for stem cell therapy in repair of fibrosed lungs. As there are no animal models that fully capture PF-disease processes, information obtained from well-designed mathematical models could be critical for development of strategies that would beneficially enhance stem cell engraftment in in vivo implants.